title: Early rise in circulating endothelial protein C receptor correlates with poor outcome in severe sepsis.
abstract: OBJECTIVE
  The endothelial protein C receptor (EPCR) negatively regulates the coagulopathy and inflammatory response in sepsis. Mechanisms controlling the expression of cell-bound and circulating soluble EPCR (sEPCR) are still unclear. Moreover, the clinical impact of EPCR shedding and its potential value to predict sepsis progression and outcome remain to be established.
  
  
  METHODS
  We investigated the time course of plasma sEPCR over the 5 first days (D) of severe sepsis in 40 patients.
  
  
  RESULTS
  No significant difference was observed when comparing sEPCR at admission (D1) to healthy volunteers and to patients with vasculitis. We report that the kinetics profile of plasma sEPCR in patients was almost stable at the onset of sepsis with no change from D1 to D4 and then a significant decrease at D5. This pattern of release was consistently observed whatever the level of sEPCR at D1. Characteristics of patients or of infections (except Gram negative) had no or little critical influence on the sEPCR profile. However, we found that sEPCR kinetics was clearly associated with patient's outcome (D28 survival). We demonstrate that a significant but moderate (<15% of basal level) and transient increase in sEPCR level at D2 is associated with poor outcome at D28.
  
  
  CONCLUSIONS
  Severe sepsis, at the onset, only triggers moderate quantitative changes in plasma sEPCR levels. Our findings suggest that in severe sepsis, an early (at D2), transient but significant increase in circulating sEPCR may be detrimental suggesting that sEPCR could provide an early biological marker of sepsis outcome.
authors.affiliation: INSERM UMR643, Institut de Transplantation et de Recherche en Transplantation, ITERT, CHU Nantes, 44000 Nantes, France. christophe.guitton@chu-nantes.fr
authors.forename: Christophe
authors.initials: C
authors.lastname: Guitton
authors.forename: Nathalie
authors.initials: N
authors.lastname: Gérard
authors.forename: Véronique
authors.initials: V
authors.lastname: Sébille
authors.forename: Cédric
authors.initials: C
authors.lastname: Bretonnière
authors.forename: Olivier
authors.initials: O
authors.lastname: Zambon
authors.forename: Daniel
authors.initials: D
authors.lastname: Villers
authors.forename: Béatrice
authors.initials: B
authors.lastname: Charreau
mesh_terms: D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood*; D000074283:Endothelial Protein C Receptor; D005260:Female; D005602:France; D006801:Humans; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D017063:Outcome Assessment, Health Care; D011956:Receptors, Cell Surface / Q000097:blood*; D018805:Sepsis / Q000503:physiopathology*; D012720:Severity of Illness Index; D014657:Vasculitis / Q000503:physiopathology
chemical_list: D015703:Antigens, CD; D000074283:Endothelial Protein C Receptor; C478370:PROCR protein, human; D011956:Receptors, Cell Surface